The daughters of Th-229 (Ac-225 and Bi-213) and other alpha-emitting radioisotopes are rapidly becoming of great interest for short range and site-specific therapy of cancers and micrometastatic disease. Pre-clinical and Phase I clinical trials involving Bi-213 are underway throughout the world focusing on treatment of acute myelogenous leukemia, prostate cancer, multiple myeloma, non-Hodgkin lymphoma, colon cancer, and other diseases (Jurcic, J. G., et al., “Targeted Alpha-Particle Immunotherapy for Myeloid Leukemia,” Blood, 100, pp. 1233-1239, 2002). Success in one or more of these trials will greatly increase demand for alpha-emitting radioisotopes and will necessitate improved methods for delivering the isotopes at clinics.
In many of the current generator systems, the production process uses an organic exchange resin. Radiolytic breakdown of these generators limits their size to a few mCi and their useful lifetime to a few days (Boll, R. A., et al., “Optimizations of Radiolabeling of Immunoproteins with Bi-213,” Radiochimica Acta, 79, pp. 145-149, 1997). Generators with loadings of up to 25 mCi have been prepared by distributing the activity throughout the resin. With this approach, shelf life of generators has been extended to a week (McDevitt, M. R., et al., “An Ac-225/Bi-213 Generator System for Therapeutic Clinical Applications: Construction and Operation,” Appl. Radiat. Isot., 50, pp. 895-904, 1999). The use of silica-based extraction chromatographic resin showed some resistance to damage by alpha-radiolysis when in combination with a broad distribution of the Ac-225 on the resin (Wu, C., et al., “An Improved Generator for the Production of Bi-213 from Ac-225” Radiochimica Acta, 79, 141-144 (1997).
For clinical applications, generators containing 60 mCi or more are typically required. However, a decrease in the performance of the resin-based Ac-225/Bi213 generators at these higher levels of radioactivity tends to occur due to radiolytic breakdown of the resins in a high radiation field. In turn, radiolytic breakdown generally results in: (1) lower yields of Bi-213, (2) undesirable higher Ac-225 breakthrough, and (3) extra processing time for purification of the Bi-213 product for incorporation into radiopharmaceutics.